Radioisotope bone scanning is the most sensitive procedure for detecting tumor metastases in bone, and is widely used for that purpose. The radioactive drugs of choice are complexes of Tc-99m with any of several phosphate derivatives. Scan quality is erratic; this problem is attributed to poorly understood differences between one lot of the drug and another, and between individual patients. The reproducibilty of these radiopharmaceuticals is hard to assess, since - despite wide clinical use - their chemical composition and purity have never been established. At least one of them has been shown to be a mixture of uncertain and perhaps variable composition. The component fractions may each have different properties, some desirable and some detrimental. For quality control in the preparation of these agents, and for an understanding of their clinical properties, new radioanalytical methods are needed which are capable of quantitating the individual fractions. We have thus far developed chromatographic methods showing multiple fractions in the bone scanning agent technetium pyrophosphate, and also in the urine of patients who have received this agent. We have also prepared single fractions of this agent in the laboratory. Funding is now sought to explore the clinical implications of this work. We propose to extend our methods to the other major agents, technetium etidronate and technetium medronate; to adapt them to plasma analysis; and to apply them to study the metabolism of bone scanning agents in order to determine the optimum composition. We expect this work to make bone scanning a more reliable means of cancer detection.